An effective vaccine should confer long lasting immunity without causing any adverse side effects or reversion to disease status. Traditional vaccines have focused on the administration of live attenuated, whole killed or non-live preparations of pathogen to the host. These vaccines have proven effective in generating both protective humoral and cellular immune responses against a number of viruses. The development of vaccines against some viral pathogens is not an easy task. This task is complicated by several factors which include the pathobiology of the pathogen and the specificity of the host immune response. Recently, a novel tool for understanding the immune component involved in these interactions has become available. This tool i.e. genetic immunization or DNA vaccination is a unique resource for the effort to develop safe and functional vaccines against a wide range of pathogens.
The Human Immunodeficiency Virus Type 1 (HIV-1) is the etiological agent for the acquired immune deficiency syndrome (AIDS). HIV-1 is a lentivirus that uses RNA to transmit its message to its target cell where it is then converted to cDNA and integrated into the target cell nucleus. Due the high rate of errors in the conversion of RNA to cDNA, HIV-1 is a highly mutable virus, which makes developing a traditional vaccine against it a difficult task. Genetic immunization, in which short DNA segments as opposed to the whole viral genome are used to immunize patients, is proving to be a safe way to vaccinate against this virus. To date, DNA vaccines have been developed against HIV-1 structural, enzymatic, and accessory genes, and tested for their ability to induce immune responses in murines and primates. A few of these vaccine constructs are currently in phase I clinical trials.
The immune mechanism(s) involved in protection against HIV-1 remains unclear. Of a spectrum of various host immune responses, induction of cell-mediated immunity could be an especially important requirement of an effective HIV-1 vaccine candidate, because cellular immunity may play a critical role in viral clearance. CTLs can target not only the gene products present in the viral particle, but also all viral gene products which are expressed during viral replication. Earlier studies have shown that in HIV-1 infected patients, control of initial viremia is associated with the presence of CD8+ T lymphocyte cellular responses. Additionally, HIV-1 positive long term non progressors and uninfected children born to HIV-1 infected mothers show very high CTL responses against HIV-1 proteins suggesting that obtaining CTL responses should be an important focus of anti-HIV vaccine development. Targeting immune responses against viral proteins through the development of specific CTL responses could aid in lowering viral load by destroying viral factories and thus lowering the establishment of initial viral load.
Primate lentiviral genomes contain genes encoding novel regulatory and accessory proteins in addition to their structural and enzymatic genes. The regulatory genes, tat and rev, and the accessory genes, nef, vif, vpr, vpu and vpx, are well conserved in primate lentiviruses, including HIV-1, HIV-2, and SIV. The well conserved nature of these genes implies that their protein products play a critical role in viral pathogenesis in vivo. Recent studies implicate the accessory genes in enhanced virion production and attribute them to the pathogenesis of HIV infection, both of which lend support to the notion that the accessory genes are actual vital components of HIV-1. These gene products represent 20% of the viral open reading frame and are immunogenic in vivo and are possibly less susceptible to mutagenesis, and thus they represent an important target for vaccine development. The development of DNA vaccines against HIV-1 accessory and regulatory genes is being researched, but the fact that these genes can potentially disrupt normal cellular activities adds an additional level of complexity to the development of anti-accessory gene DNA vaccines.
There is a need for vaccines against HIV. There is a need for compositions and methods which produce immune responses which can eliminate virally infected target cells from different clades.